Biomedical subjects

A Bartke

Publications and source records attributed to A Bartke.

At least 127 records · Page 7Linked to original sources

PubMed1994

Assessment of the role of follicle-stimulating hormone and prolactin in the control of testicular endocrine function in adult djungarian hamsters (Phodopus sungorus) exposed to either short or long photoperiod.

Exposure of adult male Djungarian hamsters (Phodopus sungorus) to a short photoperiod induces testicular atrophy. To evaluate the role of FSH and prolactin (PRL) in the control of testicular endocrine function, adult Djungarian hamsters were exposed to either a long photoperiod (16L:8D per day) or a short photoperiod (6L:18D per day) for 11 wk. After 11 wk, hamsters housed in each of these photoperiods were placed into three groups and treated s.c. daily for 7 days with 50% polyvinylpyrrolidone in saline (SAL-PVP), rat FSH (10 micrograms/hamster/day) in SAL-PVP, or ovine PRL (100 micrograms/hamster/day) in SAL-PVP. On Day 8, animals in each of these groups received i.p. injections of saline or ovine LH (0.3 microgram/g BW); 1 h later, blood was obtained by cardiac puncture under ether anesthesia. Plasma FSH, LH, PRL, androstenedione (A-dione), and testosterone levels were measured by validated RIAs. In hamsters kept in the short photoperiod, testicular weight was decreased (p < 0.001). In these animals, FSH treatment increased (p < 0.001) testicular weight, whereas PRL injections had no effect. Testicular weight in animals kept in the long photoperiod was unaffected by FSH or PRL treatment. After 12 wk of exposure to the short photo-period, circulating PRL levels were undetectable; plasma levels of FSH (p < 0.001), LH (p < 0.05), A-dione (p < 0.005), and testosterone (p < 0.001) were significantly reduced. Administration of either FSH or PRL had no influence on plasma A-dione levels in hamsters exposed to either photoperiod.(ABSTRACT TRUNCATED AT 250 WORDS)

Androstenedione↗

PubMed1994

The hamster Sertoli cell in early testicular regression and early recrudescence: a stereological and endocrine study.

Utilizing stereological techniques, the hamster Sertoli cell at Stage VII of the spermatogenic cycle was examined for early signs of regressive changes after short-term photoperiod-induced testicular regression and for early signs of stimulation after short-term photoperiod-induced recrudescence. After 4-6 weeks of exposure to short photoperiod, germ cell degeneration was prominent but there were only minimal changes in Sertoli cell structure. These included a decline in volume of multivesicular bodies and in the surface area of mitochondrial membranes and adluminal plasma membrane, while no changes were noted in the other parameters measured. Of the endocrine changes, only plasma FSH levels had declined at this time and there were virtually no significant correlations between plasma FSH levels and the various structural parameters. The general lack of Sertoli cell changes in response to a short exposure to inhibitory photoperiod in the seasonally breeding hamster is similar to the early response to hypophysectomy in the none-seasonal rat. During early photoperiod-related recrudescence, testis weight, tubular lumen volume and interstitial parameters were increased. Significantly more preleptotene spermatocytes (about a 50% increase) were present in stage VII tubules, though adluminal germ cells did not increase in number. At this time some structural features of the Sertoli cells were enhanced in volume (cytoplasm, smooth and rough endoplasmic reticulum) and surface area (outer and inner mitochondrial membranes, smooth and rough endoplasmic reticulum and the basal compartment plasma membrane). Blood levels of FSH and testosterone were increased significantly but correlated only with rough endoplasmic reticulum, suggesting that initiation of the synthetic processes was important in reestablishment of spermatogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Increased hypothalamic somatostatin expression in mice transgenic for bovine or human GH.

Acute studies of GH removal by hypophysectomy or GH replacement in adult rats have shown that GH has a positive influence on its hypothalamic inhibitory hormone somatostatin (SRIH). The present study was undertaken to assess the effect of lifelong exposure to elevated GH on the development and differentiation of SRIH-producing hypothalamic neurons, including comparison of differing GH levels and heterologous species of GH. Expression of somatostatin peptide and mRNA was evaluated using respective immunocytochemistry and in situ hybridization in brains of transgenic mice bearing constructs of either human (hGH) or bovine (bGH) linked to metallothionein (MT) promoter or bGH linked to phosphoenolpyruvate carboxykinase (PEPCK) promoter. Nontransgenic littermates served as controls. All transgenic constructs resulted in high levels of circulating heterologous GH and significantly elevated body weights. Both bGH levels and body weights were higher in PEPCK-bGH than in MT-bGH mice; mean weights were not different between MT-bGH and MT-hGH mice. Numbers of SRIH-immunoreactive neurons in the hypophysiotropic periventricular nucleus (PeN) of transgenic mice showed a two-fold increase (P < 0.01) relative to control animals; the number of SRIH-positive cells in the medial basal hypothalamus (MBH) was comparable for transgenic and control mice. Total SRIH mRNA in situ hybridization intensity also showed a two-fold increase (P < 0.05) in the PeN of all transgenic mice compared with controls, and was not elevated in the MBH. The higher levels of GH produced in PEPCK-bGH transgenic mice led to greater weight gain, but not to greater SRIH expression than in other GH-transgenic mice, suggesting that the increased SRIH cell number and mRNA in the PeN of MT-GH-transgenic mice may represent a plateau of maximal feedback stimulation. The results indicate that lifelong elevated heterologous GH in mice stimulates hypothalamic SRIH expression markedly. It is not known whether this mechanism is direct or indirect via a mediator of GH such as IGF, but the heterologous GH appears to be specific to these hypophysiotropic neurons.

Animals↗

PubMed1994

Immunoreactive substance P and neurokinin A in the hypothalamus and anterior pituitary gland of Siberian and Syrian hamsters and of rats.

In this investigation the concentrations of immunoreactive substance P and neurokinin A in the hypothalamus and anterior pituitary of the Siberian hamster were compared with those in the rat and Syrian hamster. The concentrations of immunoreactive neurokinin A in the hypothalamus of Siberian hamsters were significantly higher than those of rats and Syrian hamsters, while male Siberian hamsters had similar amounts of substance P in the hypothalamus to those of male Syrian hamsters, but had higher amounts than those in male rats. However, female Siberian hamsters and significantly higher hypothalamic concentrations of both substance P and neurokinin A than did female Syrian hamsters and rats. In the anterior pituitary glands of Siberian hamsters, concentrations of substance P and neurokinin A were markedly higher than they were in rats and even more so more in Syrian hamsters. Ovariectomy further increased tachykinin concentrations in the anterior pituitary gland of female Siberian hamsters, and this was completely prevented by oestradiol replacement. Female Siberian hamsters kept under conditions of reduced photoperiod had significantly higher tachykinin concentrations in the anterior pituitary than did animals kept under daily photoperiods of 16 h light:8 h dark. The incubation of anterior pituitaries from female Siberian hamsters with a neurokinin A receptor antagonist resulted in a partial blockade of the LH and FSH release in response to LHRH. Thus, the high concentration of tachykinins present in the anterior pituitary of the Siberian hamster may have a local role in modulating the secretion or release of gonadotrophins.

Animals↗

PubMed1994

Growth hormone (GH) binding and effects of GH analogs in transgenic mice.

Overexpression of human (h) or bovine (b) growth hormone (GH) in transgenic mice is associated with marked (2- to 12-fold) and significant increase in hepatic binding of GH and prolactin (PRL). This is due to an increase in the number of GH and PRL receptors (GHR, PRLR) per mg of microsomal protein without changes in binding affinity. Comparison of results obtained in transgenic animals expressing bGH with a mouse metallothionein (MT) or a rat phosphoenolpyruvate carboxykinase (PEPCK) promoter suggests that effects of bGH on hepatic GHR and PRLR do not require GH overexpression during fetal life and, within the dose range tested, the effects on PRLR are not dose dependent. The increase in hepatic GHR was accompanied by significant increases in plasma GH-binding protein (GHBP) and in mean residence time of injected GH. Thus, life-long elevation of peripheral GH levels alters the availability of both free GH and GHR. Site-directed in vitro mutagenesis was used to produce hGH and bGH analogs mutated within one of the sites involved in binding to GHR and PRLR. Mutating hGH to produce amino acid identity with bGH at Position 11, 18 (within Helix 1), 57, or 60 (within the loop between Helix 1 and 2) did not affect binding to GHR in vitro, or somatotropic activity in transgenic mice in vivo but reduced lactogenic activity in Nb2 cells by 22%-45%. Mutations of bGH designed to produce amino acid identity with hGH at one to four of the corresponding positions in the bGH molecule did not interfere with binding to GHR or somatotropic activity in vivo, and failed to produce significant binding to PRLR but resulted in alterations in the effects on the hypothalamic and anterior pituitary function in transgenic mice. Apparently region(s) outside the domains examined are essential for lactogenic activity of hGH, and different portions of the GH molecule are responsible for its diverse actions in vivo.

Animals↗

PubMed1994

Neuroendocrine and reproductive consequences of overexpression of growth hormone in transgenic mice.

Availability of recombinant growth hormone (GH) and development of long-acting formulations of this material will undoubtedly lead to widespread use of GH in animal industry and in medicine. GH can act, directly or indirectly, on multiple targets, but its influence on the reproductive system and on the hormonal control of reproduction is poorly understood. Overexpression of GH genes in transgenic animals provides a unique opportunity to study the effects of long-term GH excess. Transgenic mice overexpressing bovine, ovine, or rat GH (hormones with actions closely resembling, if not identical to, those of endogenous [mouse] GH), exhibit enhancement of growth, increased adult body size, and reduced life-span as well as a number of endocrine and reproductive abnormalities. Ectopic overexpression of bovine GH (bGH) driven by metallothionein or phosphoenolpyruvate carboxykinase promoters is associated with altered activity of hypothalamic neurons which produce somatostatin, loss of adenohypophyseal GH releasing hormone (GHRH) receptors, and suppression of endogenous (mouse) GH release. Elevation of plasma levels of GH (primarily bGH) and insulin-like growth factor (IGF-I) in these transgenic mice leads to increases in the number of hepatic GH and prolactin (PRL) receptors, in the serum levels of GH-binding protein (GHBP), in the percent of GHBP complexed with GH, and in the circulating insulin levels. In addition, plasma adrenocorticotropic hormone (ACTH) and corticosterone levels are elevated. Plasma levels of luteinizing hormone (LH), as well as its synthesis and release, are not consistently affected, but follicle-stimulating hormone (FSH) levels are suppressed, apparently due to pre- and post-translational effects. Pituitary lactotrophs exhibit characteristics of chronic enhancement of secretory activity, and plasma PRL levels are elevated. Prolactin responses to mating or to pharmacological blockade of dopamine synthesis are abnormal. Reproductive life span and efficiency are reduced in both sexes, with the severity and frequency of reproductive deficits being related to plasma bGH levels. Most transgenic females expressing high levels of bGH are sterile due to luteal failure. Overexpression of human GH which, in the mouse, interacts with both GH and PRL receptors leads to additional endocrine and reproductive abnormalities including stimulation of LH beta mRNA levels and LH secretion, loss of responsiveness to testosterone feedback, overstimulation of mammary glands, enhanced mammary tumorigenesis, and hypertrophy of accessory reproductive glands in males.

Animals↗

PubMed1993

Effects of the expression of bovine growth hormone on the testes and male accessory reproductive glands in transgenic mice.

The effects of physiological and excessive levels of growth hormone (GH) on reproductive functions are poorly understood, and impairment of fertility is frequently observed in transgenic animals overexpressing GH genes. The present study was undertaken to determine the effects of chronic exposure to heterologous bovine GH (bGH) on the testes and accessory reproductive glands in transgenic mice. Endocrine function of the testes was evaluated by measuring the activities of two steroidogenic enzymes, delta 5-3 beta-hydroxysteroid dehydrogenase (delta 5-3 beta-HSD) and 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD). The activities of acid phosphatase, alkaline phosphatase and beta-glucuronidase, important hydrolytic enzymes of lysosomal origin, were measured in testes, seminal vesicles and ventral prostates in normal and transgenic mice. Testicular delta 5-3 beta-HSD activity was higher in transgenic than in normal mice, while testicular 17 beta-HSD activity in transgenic mice was not altered. Acid phosphatase activity was elevated in both seminal vesicles and ventral prostates of transgenic mice, while alkaline phosphatase activity was increased only in the prostate. The activity of beta-glucuronidase was elevated in the testes, seminal vesicles and ventral prostate gland of transgenic mice. These results suggest that chronic exposure to bGH is associated with significant stimulation of some hydrolytic enzymes in the testes and in the accessory reproductive glands of transgenic mice.

17-Hydroxysteroid Dehydrogenases↗

PubMed1993

Pharmacokinetics of radioiodinated human and ovine growth hormones in transgenic mice expressing bovine growth hormone.

Pharmacokinetics of radioiodinated human growth hormone (hGH) and ovine growth hormone (oGH) were studied in normal mice and in transgenic mice carrying the bovine growth hormone (bGH) gene fused to phosphoenolpyruvate carboxykinase promoter/regulator (PEPCK-bGH). Multiexponential plasma decay curves were obtained in both normal and transgenic mice after a 125I-oGH injection and pharmacokinetic parameters were estimated by fitting blood concentration data to a three compartment model. The half-life for the rapid compartment was shorter in transgenic than in normal mice (t1/2 gamma: 1.2 +/- 0.3 vs. 2.2 +/- 0.5 min). The slow compartment had a t1/2 alpha of 160 +/- 23 min for transgenic and 70 +/- 8 min for normal mice while the middle compartment had a t1/2 beta of approximately 10 min for both groups of mice. The mean residence times were 167 +/- 24 and 55 +/- 5 min for transgenic and normal mice, respectively. Specific liver uptake of radioactivity after injection of 125I-oGH or 125I-hGH was found in both groups of animals. Specificity studies indicated that, similarly to normal mice, livers of transgenic mice possess a mixed population of somatotropic and lactogenic receptors. Uptake of labelled hGH by the liver was dose-dependent and the doses that prevented 50% of liver uptake (ED50%) were 8 and 165 micrograms per 50 g body weight for normal and transgenic mice, respectively. These in vivo results confirm and extend previous in vitro findings that a life-long excess of bGH increases hepatic somatotropic and lactogenic receptors. Since elevation in growth hormone (GH) receptors was reported to be associated with an increase in GH binding protein (GHBP), we suspect that both the increase in the mean residence time and the reduction in specific uptake of GH in the livers of transgenic mice may be the result of an increase in GHBP levels.

Animals↗

PubMed1993

In vitro effects of psychoactive and non-psychoactive cannabinoids on immature rat Sertoli cell function.

We have examined the effects of psychoactive and non-psychoactive cannabinoids on isolated immature rat Sertoli cells cultured in either serum-free or serum-containing media. Lactate accumulation by Sertoli cells in serum-free control cultures was 10 fold greater than the values obtained in control cultures exposed to serum. Under either culture condition, 3.1 micrograms/ml of delta-9-tetrahydrocannabinol (THC) or cannabinol (CBN) stimulated lactate secretion above control levels. Cannabidiol (CBD) stimulated lactate secretion in serum-containing but not in serum-free media. Using serum-free culture conditions, we next studied the in vitro effects of combinations of THC and either epinephrine or FSH on lactate and transferrin secretion by immature rat Sertoli cells. Co-incubation of 0.1 microM epinephrine with 0.8 or 3.1 microgram/ml THC significantly stimulated lactate secretion when compared to epinephrine or THC alone, while only the high THC dose increased transferrin secretion. Moreover, co-incubation of FSH (1 micrograms/ml) with THC (0.8 or 3.1 micrograms/ml), significantly stimulated both lactate and transferrin production by immature rat Sertoli cells. These results add to the growing evidence that cannabinoids can exert direct effects on Sertoli cell function and modulate their responses to physiological stimuli.

Animals↗

PubMed1993

1,25(OH)2 vitamin D3 binding sites in male sex organs of the Siberian hamster (Phodopus sungorus). An autoradiographic study.

Using autoradiography, binding sites for 1,25(OH)2 vitamin D3 are found in certain genital organs of male Siberian hamsters (Phodopus sungorus), in particular in basal epithelial cells and fibroblasts of the lamina propria of prostate glands. Scattered labeled cells are also present in the epithelium of coagulation and urethral glands. In contrast to the findings in mice, under the conditions of the experiment, 1,25(OH)2 vitamin D3 binding sites are not recognizable in other accessory sex glands and gonads. The frequency of basal epithelial cells with [3H]1,25(OH)2 vitamin D3 nuclear binding is higher in regressed dorsal prostate glands of animals living in short photoperiods. The data suggest that 1,25(OH)2 vitamin D3 may promote proliferation and differentiation in basal epithelial cells, modulated by the seasonal and functional status of the animal.

Animals↗

PubMed1993

Induction of endogenous insulin-like growth factor-I secretion alters the hypothalamic-pituitary-testicular function in growth hormone-deficient adult dwarf mice.

To evaluate the influence of growth hormone (GH) on hypothalamic-pituitary-testicular function, GH-deficient adult male Ames dwarf mice were treated (s.c.) twice daily for 8 days with either vehicle or bovine GH (25 micrograms/injection/mouse). Normal male siblings treated with vehicle served as controls. Two in vivo experiments were conducted. In experiment 1, on Day 8, mice were treated (i.p.) with either saline or LHRH (1 ng/g b.w.) in saline. Fifteen minutes later, blood was obtained via heart puncture to assess plasma insulin-like growth factor-I (IGF-I), LH, and testosterone (T) levels by RIAs. In experiment 2, on Day 7, mice were bilaterally castrated and received injections of either oil or T propionate (1 microgram/g b.w.) in oil. Eighteen to twenty hours later, blood was obtained as in experiment 1, and plasma IGF-I and LH levels were determined. In addition to these in vivo experiments, testicular androstenedione and T responses to hCG stimulation in vitro were evaluated. Administration of GH to dwarf mice increased (p < 0.001) plasma IGF-I levels, whereas IGF-I was not detectable in control dwarf mice. Plasma IGF-I concentrations were higher in normal mice than in treated dwarf mice. Basal LH levels were lower (p < 0.025) in dwarf mice than those in normal mice. In dwarf mice, GH treatment increased (p < 0.001) plasma LH levels. The effect of LHRH on LH secretion was increased (p < 0.001) in dwarf mice pretreated with GH, but this LH response was lower than in normal siblings that received vehicle only.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Catecholamines stimulate testicular steroidogenesis in vitro in the Siberian hamster, Phodopus sungorus.

We have examined direct effects of catecholamines on testicular testosterone production in a seasonally breeding species, the Siberian hamster, Phodopus sungorus. Testicular parenchyma from gonadally active long photoperiod (LD)-exposed and gonadally regressed short photoperiod (SD)-exposed animals was incubated for 6 h with norepinephrine, epinephrine, beta-adrenoceptor agonist isoproterenol, or alpha-adrenoreceptor agonist phenylephrine (all at 10 microM), as well as with various concentrations of norepinephrine (10 nM-10 microM), and 10 microM norepinephrine with or without hCG (0.7, 3.1, and 12.5 mIU/ml). In addition, effects of alpha-adrenoreceptor antagonist prazosin and beta-adrenoreceptor antagonist propranolol (50 microM) were tested in the incubations containing 10 microM norepinephrine. In the incubations of testes from both LD and SD Siberian hamsters, norepinephrine was most effective in stimulating testosterone production, followed by epinephrine and phenylephrine, while isoproterenol failed to increase testosterone accumulation. The stimulatory effects of norepinephrine were dose-dependent and were prevented by coincubation with prazosin, but not affected by coincubation with propranolol. In combination with various doses of hCG, norepinephrine failed to stimulate testosterone production above the levels obtained with hCG alone. These data indicate that the testicular receptors mediating the action of catecholamines on testicular steroidogenesis in Phodopus sungorus are of the alpha 1-subtype, a result in accordance with a previous study in the golden hamster. However, the results of the present study are strikingly different from the findings obtained in the golden hamster in terms of the effects of photoperiod on the responsiveness of testicular steroidogenesis to catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Gonadotropin secretion, synthesis, and gene expression in two types of bovine growth hormone transgenic mice.

Expression of the mouse metallothionein-I (MT) promoter/bovine growth hormone (bGH) or the phosphoenolpyruvate carboxykinase (Pepck) promoter/bGH fusion genes in male transgenic mice is associated with alternations in adenohypophyseal function and fertility. To determine the effects of these gene constructs on gonadotropin synthesis and secretion, we have examined basal and GnRH-stimulated LH and FSH release in vitro using static incubations and perifusions of the pituitary; we have also examined pituitary content of LH, FSH, LH beta mRNA, and FSH beta mRNA in MT/bGH and Pepck/bGH transgenic mice as well as in normal mice. In addition, we have measured LH and FSH release from normal pituitaries transplanted under the kidney capsules of Pepck/bGH transgenic or normal mice. We found that in Pepck/bGH transgenic mice, pituitary contents of FSH and FSH beta mRNA were reduced, while FSH release in vitro in pituitary incubations and perifusions was increased. Steady-state levels of LH beta mRNA as well as LH responses to GnRH in perifusions were reduced; LH release in incubations and pituitary LH content were not changed; and basal LH secretion in perifusions was increased. In MT/bGH transgenic mice, in which peripheral bGH levels are much lower than in Pepck/bGH mice, similar trends were observed, but most of the apparent differences between transgenic and normal animals were not statistically significant. When normal pituitaries were transplanted under the kidney capsules of Pepck/bGH transgenic mice, the expected decrease in LH and FSH secretion was attenuated and the response to GnRH stimulation was lost.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Sentinels of Leydig cell structural and functional changes in golden hamsters in early testicular regression and recrudescence.

The seasonally breeding hamster model was used to assess changes associated with Leydig cell activity and inactivity. Specifically, parameters of Leydig cell structure and function were studied to determine the early changes seen in seasonally breeding golden hamsters in photoperiod-induced gonadal regression and photoperiod-induced gonadal recrudescence. Time intervals used to characterize early regression and recrudescence were selected with the objective of determining the most sensitive parameters characterizing functional transitional states. In early regression, plasma levels of follicle-stimulating hormone (FSH) but not luteinizing hormone (LH) or testosterone were reduced significantly. Regressive structural changes included decreases in volume of the interstitium, total number of Leydig cells, blood vessels, and the seminiferous tubules and tubular lumen. A decrease in volume, but not numbers of Leydig cells, was accompanied by decreases in volume of Leydig cell tubular smooth endoplasmic reticulum (t-ER), Golgi complex, and the peroxisomes and decreases in surface area of the inner mitochondrial membrane and t-ER, suggesting that early Leydig cell changes are restricted primarily to organelles associated with steroid biosynthesis. In early recrudescence, at a time when there was an increase in the number of germ cells in the basal compartment, blood levels of LH, FSH and testosterone were all increased. There were increases in testicular weight, volume, seminiferous tubular lumen, blood vessel and interstitial volumes. Leydig cells increased in size as a result of increases in nuclear, nucleolar and cytoplasmic volumes, while Leydig cell numbers did not increase. At the subcellular level there were increases in the surface areas of the cell, mitochondrial membranes and cisternal endoplasmic reticulum (sparsely populated with ribosomes). Unlike the changes seen in early degeneration when steroid synthetic organelles were initially affected, the changes in early recrudescence indicate that Leydig cells must first rebuild their synthetic machinery (nucleus, nucleolus and rough endoplasmic reticulum) that, at a later time, will reconstitute the cell's steroidogenic machinery. Correlation of hormonal parameters with structural parameters did indicate a relationship between hormonal parameters and steroid secreting organelles. Correlations were strongest with testosterone but, surprisingly, plasma FSH levels correlated more strongly with many structural parameters of the Leydig cell than did the levels of LH. Since FSH receptors are not present on Leydig cells, these data add to the growing data suggesting a role for factors originating from the seminiferous tubule in modulation of Leydig cell function.

Animals↗

PubMed1993

Vitamin D (soltriol) target cells in the harderian gland of the Siberian hamster (Phodopus sungorus).

Harderian glands of female and male Siberian hamsters (Phodopus sungorus) were studied after a subcutaneous injection of 3H-dihydroxycholecalciferol (vitamin D, soltriol). Autoradiograms revealed the presence of nuclear concentration of the hormone in certain alveolar cells and in myoepithelial cells. The proportion of labeled cells varied between 5.5 and 19% of the total cell number, with an average of 9.5% in female and 12.4% in male hamsters. The data suggest that the functions of the Harderian gland could undergo seasonal changes under the control of vitamin D.

Animals↗

PubMed1993

Effects of age and endogenously secreted human growth hormone on the regulation of gonadotropin secretion in female and male transgenic mice expressing the human growth hormone gene.

In aging rats and humans, GH secretion is reduced. In transgenic mice bearing the human (h) GH gene, hGH is secreted during the entire lifespan. To evaluate the effects of endogenously secreted hGH on age-related changes in hypothalamic-pituitary function, the following two experiments were conducted in young (2.5-4 months of age) and old (11-14 months of age) female and male transgenic mice expressing the hGH gene and their normal siblings. In Exp I, young and old female transgenic mice and their normal siblings were ovariectomized. On days 8 and 9 after ovariectomy, mice were injected (sc) with oil or primed with 0.5 micrograms estradiol benzoate (EB) in oil, 24 h later treated with 10 micrograms EB/100 g BW, and a day later bled for the determination of FSH, LH, PRL, and hGH levels by RIAs. In Exp II, young and old male transgenic mice and their normal littermates were castrated and injected with either peanut oil or testosterone propionate (TP; 1 microgram/g BW) in oil. Blood samples were obtained 18-20 h after oil or TP injection. Plasma FSH, LH, PRL, and hGH levels were measured by RIAs. hGH was present in the circulation of young and old transgenic mice, but not in normal siblings. Circulating FSH and LH levels were significantly lower in ovariectomized young and old transgenic mice than in similarly treated young and old normal siblings. The suppressive effect of EB on LH secretion was reduced in ovary-ablated young and old transgenic mice. The PRL response to EB treatment was increased (P < 0.005) in old ovariectomized transgenic mice. In the male, the castration-induced increase in plasma LH levels was higher (P < 0.05) in young transgenic mice. Administration of TP failed to suppress the absolute plasma LH levels in castrated young and old transgenic mice. However, the percent decrease in circulating LH levels was lower in young and old transgenic mice. The castration-induced increase in FSH secretion was reduced (P < 0.005) in aged transgenic mice. The effects of TP on plasma FSH levels were similar to its effects on LH secretion. Gonad-ablated young and old transgenic mice of both sexes are hypoprolactinemic. These observations demonstrate that endogenously secreted hGH modulates gonadotropin and PRL secretion in young and old mice bearing the hGH gene and indicate that the changes in the hypothalamic-pituitary system of mice expressing the hGH gene are similar to those observed in aging human subjects.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

PubMed1993

Gonadotropin secretion, synthesis, and gene expression in human growth hormone transgenic mice and in Ames dwarf mice.

The expression of the mouse metallothionein-I (MT) promoter/human GH (hGH) fusion gene leads to reduced fertility and increased plasma LH levels in male MT/hGH transgenic mice. To determine the effects of hGH on gonadotropin synthesis and release, we have examined basal and GnRH stimulated LH and FSH release in pituitary incubations and perifusions; and pituitary content of LH, FSH, LH-beta messenger RNA (mRNA), and FSH-beta mRNA in MT/hGH transgenic males and in their normal littermates. For comparison, similar studies were performed in GH and PRL deficient Ames dwarf mice in which plasma gonadotropin levels are known to be reduced. We have also measured the LH and FSH release from normal pituitaries transplanted under the kidney capsule of MT/hGH transgenic or normal mice. We found that in MT/hGH transgenic mice, there were parallel increases in unstimulated and GnRH stimulated LH release from pituitary incubation, in pituitary LH content and in LH-beta mRNA levels. In pituitary perifusion, the basal LH secretion was elevated, whereas LH responses to GnRH pulses were not altered. In transgenic males, FSH-beta mRNA was increased, whereas basal and GnRH-stimulated FSH release and pituitary FSH content did not differ from their normal controls. After normal pituitaries were transplanted to kidney capsules of MT/hGH transgenic mice, the expected decrease in LH and FSH secretion was attenuated and the responsiveness to GnRH stimulation was maintained. In Ames dwarf mice, all gonadotropin content and release, as well as pituitary beta-mRNA contents were decreased. We conclude that in MT/hGH transgenic mice, the expression of LH-beta and FSH-beta gene is increased. In addition, there is a translational or posttranslational inhibitory influence on FSH synthesis. Although our previous studies suggest that the effects of hGH gene expression on LH and FSH release are exerted primarily at the hypothalamic level, the present results suggest existence of GnRH unrelated peripheral factors which can directly stimulate pituitary gonadotropin synthesis and release. In Ames dwarf mice, the deficiency of GH and PRL, as well as TSH, is associated with decreased LH-beta and FSH-beta gene expression which may account for the reduction in plasma gonadotropin levels.

Animals↗

PubMed1993

Multiple isoforms of 3 beta-hydroxysteroid dehydrogenase/delta 5-->4-isomerase in mouse tissues: male-specific isoforms are expressed in the gonads and liver.

Multiple isoforms of 3 beta-hydroxysteroid dehydrogenase/delta 5-->4-isomerase (3 beta HSD) are expressed in various mouse tissues in a tissue-specific, sex-specific, and developmental manner. Three distinct immunoreactive species [molecular masses, 47, 44, and 42 kilodaltons (kDa)] are detectable by Western immunoblot analysis using a 3 beta HSD antiserum. Different immunoreactive isoforms are expressed in steroidogenic (44 and 47 kDa in gonads) and nonsteroidogenic (42 and 47 kDa in liver and kidney) tissues. Two of these isoforms are sex-specific in the gonads (47 kDa) and liver (42 kDa), because they are detectable only in male mice. Sex-specific expression in the liver is developmentally regulated. Low levels of this male-specific hepatic isoform are first detectable at 23-25 days of age, but its level of expression increases progressively during sexual maturation to adult levels. NAD(+)-dependent 3 beta HSD activity is detectable in homogenates of all tissues examined, but the kinetic characteristics of this activity differ among tissues and are sexually dimorphic in the liver. Apparent Michaelis constants for dehydroepiandrosterone are much lower in steroidogenic (0.24 +/- 0.07 microM for testis) than in nonsteroidogenic (range, 10-100 microM for liver and kidney) tissues and are lower in male mouse liver (16 +/- 1 microM) than in female mouse liver (82 +/- 20 microM). Oligonucleotides with unique sequences but encoding homologous regions of the mouse type I, II, and III 3 beta HSD cDNAs were used for Northern blot analyses. A type I oligomer hybridizes with RNA from steroidogenic (adrenal, ovary, and testis) tissues, and a type III oligomer hybridizes with RNA from nonsteroidogenic (liver and kidney) tissues. A type II oligomer, however, hybridizes specifically with RNA from testis and liver of male mice, tissues that express a male-specific 3 beta HSD. These results suggest that type II-like transcripts may encode a 47-kDa sex-specific 3 beta HSD in testis and a 42-kDa sex-specific 3 beta HSD in liver of male mice. It is unclear how many members of subfamilies of the 3 beta HSD gene family will be discovered. The mouse may prove to be a valuable experimental model, as this is the first species in which multiple immunoreactive isoforms can be identified in a single tissue. This multiplicity makes it difficult to correlate the size and number of immunoreactive isoforms with the diverse kinetic characteristics of NAD(+)-dependent 3 beta HSD activities in tissue homogenates and to develop isoform-specific probes.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗